Visualization of hydrogen atoms in a perdeuterated lectin-fucose complex reveals key details of protein-carbohydrate interactions.

Carbohydrate-binding proteins from pathogenic bacteria and fungi have been shown to be implicated in various pathological processes, where they interact with glycans present on the surface of the host cells. These interactions are part of the initial processes of infection of the host and are very important to study at the atomic level. Here, we report the room temperature neutron structures of PLL lectin from Photorhabdus laumondii in its apo form and in complex with deuterated L-fucose, which is, to our knowledge, the first neutron structure of a carbohydrate-binding protein in complex with a fully deuterated carbohydrate ligand. A detailed structural analysis of the lectin-carbohydrate interactions provides information on the hydrogen bond network, the role of water molecules, and the extent of the CH-π stacking interactions between fucose and the aromatic amino acids in the binding site

Terminology of bioanalytical methods (IUPAC Recommendations 2018)

Recommendations are given concerning the terminology of methods of bioanalytical chemistry. With respect to dynamic development particularly in the analysis and investigation of biomacromolecules, terms related to bioanalytical samples, enzymatic methods, immunoanalytical methods, methods used in genomics and nucleic acid analysis, proteomics, metabolomics, glycomics, lipidomics, and biomolecules interaction studies are introduced

Adhesive glycostrategies from opportunistic filamentous fungi

International audienc

Upalni i hematotoksični potencijal metabolita plijesni Stachybotrys chartarum (Ehrenb.) Hughes u zatvorenim prostorijama

Mould Stachybotrys chartarum (Ehrenb.) Hughes is known to pose a health risk in indoor environments. Most of its strains can produce several intra- and extracellular trichothecene mycotoxins. Complex secondary metabolites of stachybotrys isolates from mouldy dwellings/public buildings in Slovakia were intratracheally instilled in Wistar male rats (4 μg in 0.2 mL of 0.2 % dimethylsulphoxide; diacetoxyscirpenol as the positive control). After three days, haematological parameters were measured in peripheral blood and infl ammatory response biomarkers in bronchoalveolar lavage fl uid (BALF), and the results were statistically analysed. Exometabolites proved to suppress red blood cell (RBC), decreasing the total RBC count, haemoglobin, and haematocrit. The exposed rats showed signifi cantly higher total BALF cell count, indicating infl ammation, lower alveolar macrophage counts, and increased granulocyte count related to the BALF cells. Due to haematotoxic and infl ammation-inducing properties, metabolites of S. chartarum can cause damage to the airways and haematological disorders in occupants of mouldy buildings.Plijesan Stachybotrys chartarum (Ehrenb.) Hughes poznata je kao rizični mikroorganizam u zatvorenim prostorijama. Većina njezinih sojeva može proizvesti nekoliko unutarstaničnih i izvanstaničnih trikotecenskih mikotoksina. Muškim Wistar štakorima instilirani su intratrahealno kompleksni sekundarni metaboliti stahibotrisa izolirani iz stambenih i javnih zgrada u Slovačkoj zahvaćenima plijesni (4 μg na 0,2 mL 0,2 %-tnog dimetilsulfoksida; dok se diacetoksiscirpenol rabio kao pozitivna kontrola). Tri dana kasnije izmjereni su hematološki parametri u perifernoj krvi te biopokazatelji upalnoga odgovora u bronhoalveolarnome ispirku te su rezultati obrađeni statistički. Pokazalo se da egzometaboliti suprimiraju eritrocite, smanjujući njihov ukupni broj, hemoglobin i hematokrit. Izloženi štakori imali su značajno veći broj stanica u bronhoalveolarnome ispirku, što upućuje na upalu, dok im je broj alveolarnih makrofaga bio manji, a broj granulocita povezanih sa stanicama u ispirku veći. Zbog svojih hematotoksičnih i upalnih svojstava S. chartarum može dovesti do oštećenja dišnih putova i poremećaja u krvotvornome sustavu osoba koje žive i/ili rade u zgradama zahvaćenima tom plijesni

Burkholderia cenocepacia BC2L-C Is a Super Lectin with Dual Specificity and Proinflammatory Activity

Lectins and adhesins are involved in bacterial adhesion to host tissues and mucus during early steps of infection. We report the characterization of BC2L-C, a soluble lectin from the opportunistic pathogen Burkholderia cenocepacia, which has two distinct domains with unique specificities and biological activities. The N-terminal domain is a novel TNF-α-like fucose-binding lectin, while the C-terminal part is similar to a superfamily of calcium-dependent bacterial lectins. The C-terminal domain displays specificity for mannose and l-glycero-d-manno-heptose. BC2L-C is therefore a superlectin that binds independently to mannose/heptose glycoconjugates and fucosylated human histo-blood group epitopes. The apo form of the C-terminal domain crystallized as a dimer, and calcium and mannose could be docked in the binding site. The whole lectin is hexameric and the overall structure, determined by electron microscopy and small angle X-ray scattering, reveals a flexible arrangement of three mannose/heptose-specific dimers flanked by two fucose-specific TNF-α-like trimers. We propose that BC2L-C binds to the bacterial surface in a mannose/heptose-dependent manner via the C-terminal domain. The TNF-α-like domain triggers IL-8 production in cultured airway epithelial cells in a carbohydrate-independent manner, and is therefore proposed to play a role in the dysregulated proinflammatory response observed in B. cenocepacia lung infections. The unique architecture of this newly recognized superlectin correlates with multiple functions including bacterial cell cross-linking, adhesion to human epithelia, and stimulation of inflammation

Combining fold recognition and exploratory data analysis for searching for glycosyltransferases in the genome of Mycobacterium tuberculosis

International audienc

Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood

BACKGROUND: In the risk assessment of PCDDs, PCDFs, and dioxin-like (DL) PCBs, regulatory authorities support the use of the toxic equivalency factor (TEF)-scheme derived from a heterogeneous data set of the relative effect potency (REPs) estimates. OBJECTIVES: We sought to determine REPs for dioxin-like compounds (DLCs) using expression of cytochrome P450 (CYP) 1A1 and 1B1 mRNA in human peripheral blood mononuclear cells representing two different pathways. METHODS: We used a sex and age adjusted regression-based approach comparing the strength of association between each DLC and the cytochrome P450 (CYP) 1A1 and 1B1 mRNA expression in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. RESULTS: We calculated REPs based on CYP1A1 expression for 4 PCDDs, 8 PCDFs, and 1 PCB congener, and based on CYP1B1 expression for 5 PCDFs and 11 PCB congeners. REPs from CYP1A1 correlated with REPs previously derived from thyroid volume (ρ=0.85; p<0.001) and serum FT4 (ρ=0.77; p=0.009). The 13 log REPs from CYP1A1 correlated with log WHO-TEFs (r=0.63; p=0.015) and 11 log PCB REPs with PCB consensus toxicity factors (CTFs) for compounds with WHO-TEFs (r=0.80; p=0.003). The complete set of derived 56 log REPs correlated with the log CTFs (r=0.77; p=0.001) and log WHO-TEFs (r=0.81; p<0.001). CONCLUSIONS: REPs calculated from thyroid and cytochrome P450 endpoints realistically reflect human exposure scenarios because they are based on human chronic and low-dose exposures. While the CYP 1A1 seems more suitable for toxicity evaluation of PCDD/Fs, the CYP 1B1 is more apt for PCDFs and PCBs and reflects different pathways

Bioanalytical Chemistry

This chapter provides a terminology of bioanalytical chemistry in general and analysis of biomacromolecules in particular. The vocabulary given in this chapter is largely taken from Labuda et al. “Terminology of bioanalytical methods (IUPAC Recommendations 2018)”,1 which becomes the immediate source reference for definitions of terms in this chapter that are not otherwise attributed. Reference to secondary sources follow the entry as “see also:” Terms are taken from the IUPAC Recommendations published in 1994 covering mostly the analytical terminology related to body fluids, enzymology, and immunology.2 Selected terms related to bioanalysis are included within recommendations and reports devoted to the unit “katal”,3 biotechnology,4 clinical chemistry,5 toxicology,6,7 medicinal chemistry,8,9 proteomics,10 electrochemical biosensors,11,12 and physical organic chemistry.13 Definitions of some terms have been updated here with respect to new reports and considerations, and a number of new terms has been introduced particularly on the topics of “–omics”, DNA analysis and studies of the interactions between biomolecules. Terms from earlier IUPAC Recommendations that are replaced by ref. 1 are not otherwise referenced but can be found as references in ref. 1